Classification Criteria For Systemic Sclerosis Research Articles

Epigastric discomfort in a young woman: unveiling a case of CREST syndrome

Introduction and Importance: CREST syndrome is a clinical condition, seen in relation with systemic sclerosis, which meets at least three of its five clinical features: calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Three of these clinical features (Raynaud’s phenomenon, sclerodactyly and esophageal dysmotility) are often present in classical subsets of SSc: limited and diffuse, and their presence alone in association does not define CREST syndrome. The laboratory findings (autoimmunity) are the most crucial for diagnosis. Hence, a comprehensive clinical assessment, autoimmune investigations should be performed to make the final diagnosis of CREST Syndrome, as per the criteria states. We describe a case involving a 34-years-old female who was diagnosed with CREST Syndrome during medical evaluation of her epigastric discomfort. Case Presentation: We present the case of a 34-year-old female, presented with clinical cutaneous and gastrointestinal manifestations along with autoantibody production when investigated, which was compatible with the diagnosis of a limited form of systemic sclerosis (SSc), CREST Syndrome. Clinical Discussion: In the absence of a diagnostic test to prove the absence or presence of SSc, the diagnosis is based on a combination of clinical and laboratory findings. Thus, a detailed clinical history and careful physical examination are required. With regard to the diagnosis, an updated classification criteria for SSc as published by ACR/EULAR in 2013 is used and helped us to reach the final diagnosis. Conclusion: CREST syndrome, a rare clinical entity, warrants consideration by primary physicians while evaluating it. Despite its rarity, inclusion in differentials is essential to prevent worsening of the condition and having further complications. Heightened awareness among healthcare providers is pivotal for prompt recognition and appropriate management.

A case of Buerger's disease with vasculopathy and skin fibrosis requiring differential diagnosis from systemic sclerosis.

Buerger's disease is characterized by peripheral ischemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis. The patient exhibited Raynaud's phenomenon in year X-3, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year X. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis, several findings in this case were atypical for systemic sclerosis, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation.

Assessment of Skin by High Frequency Musculoskeletal Ultrasound in Egyptian Patients with Systemic Sclerosis

Abstract Background Fibrotic involvement of the skin is a cardinal feature of systemic sclerosis (SSc). The extent of skin involvement is associated with internal organ involvement with severe disease course and poor prognosis. SSc skin involvement is characterized by three phases in temporal sequence: edematous, fibrotic, and atrophic. A palpation-based semi- quantitative score, the modified Rodnan skin score (mRSS) is widely used for the assessment of skin involvement. It is a quick, noninvasive clinical assessment that correlates with histological grading of skin fibrosis. However, it lacks the sensitivity to differentiate between clinically indistinguishable pathological phases such as inflammatory edema vs. established fibrosis. More objective approaches to measure skin involvement imaging have been developed in the past decades.In our study, we review the use of ultrasound for the assessment of early changes in skin thickness and echogenicity in patients with SSc, focusing. mainly on high frequency ultrasound. Aim of the Work to evaluate the role of high frequency ultrasound (HFUS) of skin in assessment of early changes in skin thickness and echogenicity in patients with SSc. Patients and Methods Our study is a cross-sectional, observational study involving homogenous groups consisting of 23 SSc patients and 21 healthy age and sex matched controls. Patients who fulfilled the 2013 ACR/EULAR Classification Criteria for SSc. Results DT was evaluated by both mRSS and HFUS at 5 skin areas in both patients and control. We found statistically significant difference between the two studied groups as regards in area 1 longitudinal (P = 0.017) and area 1 in transverse (P = 0.038), tendency to significance in area 2 (P = 0.054). Subclinical dermal involvement was detected by HFUS even in the skin areas in patients who had a normal local MRSS ( These areas were not planned to be assessed by high frequency ultrasound but added to the five areas to be assessed to evaluate for ultrasound detected subclinical involvement of skin in SSc patients ). In particular, DT was highly significantly greater in patients with area with Rodnan zero score at dorsum of hand than in healthy subjects (longitudinal and transverse) (P < 0.001, 0.005 ) respectively. Similar changes at the level of echogenicity occurred in determination of the stage of the disease, with increased skin thickness and decreased echogenicity occurring early and during skin disease activity due to edema; and decrease skin thickness and increased echogenicity occurring late with skin atrophy Conclusion that high frequency ultrasound is a useful tool in assessment of skin pathologic changes (even subclinical changes) in terms of thickness and echogenicity in patients with SSc both at disease onset and during follow up of response to therapy and disease stage. Moreover, it could be a useful screening tool with definite cutoff values at certain areas that differentiate normal from pathologic skin thickness.

Late-age onset systemic sclerosis—clinical and serological characteristics

The clinical course and serological profile of the late-age onset systemic sclerosis (LAO SSc) and the early-age onset SSc (EAO SSc) was compared. The study enrolled 157 patients that fulfilled the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria for systemic sclerosis (SSc). Among them, 69 had diffuse cutaneous SSc (dcSSc) and 88 limited cutaneous SSc (lcSSc). Within this population, 39 patients developed the disease over the age of 60 years old (LAO SSc) and 118 prior to that age (EAO SSc). The subtype of SSc, the incidence of internal organ involvement, the prevalence of malignancy, mortality, and serological profile were compared between both groups. The LAO SSc was observed in 39 of total 157 patients with SSc and exhibited a notably higher prevalence of pulmonary arterial hypertension (p = 0.014), heart involvement (p = 0.0014), and renal involvement (p = 0.0002). The occurrence of arthralgias was less common in the LAO SSc group (p = 0.02) than in the EAO SSc group. Furthermore, in the LAO SSc group, the prevalence of anti –RNA polymerase III antibodies (p = 0.008) and antiPM/Scl antibodies (p = 0.048) were significantly lower than in the EAO SSc group. On the other hand, higher anti-Th/To antibody levels (p = 0.014) were recorded in the LAO SSc group. Approximately 25% of SSc patients experienced a delayed onset of the disease after the age of 60 years old. Some clinical and serological features of late-onset SSc were markedly different from that in early-onset disease. Particularly noteworthy is the fact that involvement of internal organs such as heart and kidneys, as well as pulmonary arterial hypertension were much more often observed among patients with LAO SSc which in our suggestion may be referred to age-related co-morbidities.Key Points• Significant differences in clinical and serological profile of the disease were found between late-age onset (LAO) and early-age onset (EAO) SSc.• Incidence of dcSSc as well as prevalence of anti–RNA polymerase III and anti-PM/Scl antibodies were found to be lower in patients over 60 years old compared to those before 60, but regardless of the age of the disease onset.• Internal organ morbidity, notably pulmonary arterial hypertension, renal impairment and heart disease were significantly more common in elder SSc patients as well as in those with late disease onset.• These findings may suggest an impact of age-related co-morbidities on the course of late-age onset SSc.

Arthritis in patients with very early systemic sclerosis: a comprehensive clinical and prognostic analysis.

Arthritis is associated with a worse prognosis in established systemic sclerosis (SSc). However, knowledge about its relevance in very early SSc (veSSc) is scarce. We aimed to assess the prevalence and phenotype of arthritis, as well as its prognostic impact, in patients with veSSc. We analysed patients with veSSc, defined as presence of Raynaud's phenomenon and/or at least one of: puffy fingers, antinuclear antibodies (ANA), abnormal capillaroscopy, not fulfilling the ACR/EULAR classification criteria for SSc at baseline. We investigated associations between arthritis and clinical parameters, followed by a longitudinal analysis to investigate arthritis as a potential predictor of progression towards established SSc. We included 159 patients, of whom 108 had at least one follow-up visit. SSc-related arthritis occurred in 22/159 (13.8%) patients at baseline. Arthritis was mostly seronegative, symmetrical, oligo- or polyarticular, non-erosive, and rarely associated with elevation of inflammatory markers. More than half of the patients needed treatment with DMARDs. Anti-centromere antibodies were negatively associated with arthritis (OR: 0.707, 95% confidence interval 0.513-0.973, p = 0.033). Overall, 43/108 (39.8%) patients with follow-up progressed to established SSc during the observation time. Arthritis was not a significant predictor for progression to established SSc in a multivariable Cox regression. In this first comprehensive analysis, we found a similar prevalence of arthritis in veSSc as seen in established SSc. Moreover, the use of DMARDs indirectly suggests a relevant disease burden.

Dysregulation of circulating collagen turnover markers in very early systemic sclerosis

ObjectiveClinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already...

P135 Association of Serum Anti-Muscarinic 3 Antibodies with Gastrointestinal Disease in Systemic Sclerosis

Abstract Background/Aims Gastrointestinal (GI) complications of systemic sclerosis (SSc) are frequent and debilitating with symptoms ranging from reflux to faecal soilage. The pathogenesis of GI disease in SSc is poorly understood. Circulating antibodies against Muscarinic type 3 Receptors (anti-M3R) have been implicated in GI smooth muscle dysfunction and neural activation impairment. We examine whether anti-M3R antibodies associate with objective measures of gastrointestinal symptoms. Methods Sera were collected from SSc patients fulfilling the American College of Rheumatology (ACR) classification criteria for SSc. Healthy control (HC) sera were obtained from age-matched volunteers. SSc patients completed the UCLA GIT 2.0 (UCLA GIT) questionnaire. Serum anti-M3R antibodies were measured using specific enzyme-linked immunosorbent assay (ELISA)(CellTrend GmbH, Germany). SSc sera had elevated anti-M3R antibodies if the concentration exceeded two standard deviations above the mean of HC sera. Statistical comparisons were made using Fisher’s exact test and two sample t-test. Results Sera from 40 SSc patients and five HC were assayed for anti-M3R antibodies. Anti-M3R antibody was higher in SSc patients in comparison to HC (1547 vs 1183U/ml, p = 0.33). Anti-M3R antibody levels were significantly elevated in nine (23%) SSc patients. Cohort characteristics were compared based on anti-M3R antibody levels for SSc patients (Table 1). Group demographics were similar in gender, age and disease duration. There was a trend for higher anti-M3R antibodies in limited compared with diffuse cutaneous SSc subset (66.7 vs 32.2, p = 0.12). Although there was no significant association between Anti-M3R antibody level and GIT score (r = 0.014 p = 0.51), SSc patients with elevated anti-M3R antibody did report numerically more severe reflux symptoms (1.24 vs 0.8, p = 0.23) and fewer lower GI domains of severe soilage (0.56 vs 0.87, p = 0.37) and constipation (0.28 vs 0.52, p = 0.2). Conclusion These results show that there is a subset of SSc patients with elevated anti-M3R antibodies which could be pathogenic by perturbing cholinergic neurotransmission in the GI tract. The trend observed of elevated anti-M3R antibodies with more severe GI symptoms warrants further exploration in a larger cohort of SSc. If confirmed, our findings provide mechanistic rationale for reported benefit from intravenous immunoglobulin on symptom severity in SSc GI disease. Disclosure E. Roblin: None. C. Beesley: None. R. Maclean: None. F. Ahmed: None. C. Murray: None. V.H. Ong: None. C. Denton: Consultancies; C.P.D. has received consulting fees from Arxx Therapeutics, Roche, Janssen, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Boehringer Ingelheim, CSL Behring and Acceleron. Honoraria; C.P.D. has received honoraria from Janssen, Boehringer Ingelheim, and Corbus. Grants/research support; C.P.D. has received research grants to the institution from Servier, Horizon, Arxx Therapeutics and GlaxoSmithKline.

Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies

IntroductionTh/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. MethodsILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. ResultsFifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. ConclusionsOnly a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies.

Des taux élevés d’auto-anticorps anti-topo-isomérase-1 sont associés à l’extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique

BackgroundAnti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. MethodsWe conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. ResultsFifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). ConclusionATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.

Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 ( n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 ( n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 ( n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 ( n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

Tomographic Fibrosis Score in the Patients with Systemic Sclerosis-Associated Interstitial Lung Disease.

Various visual semi-quantitative staging systems based on high-resolution computed tomography are used to evaluate inflammatory rheumatologic disease-associated interstitial lung disease. We aimed in this retrospective study to evaluate whether tomographic fibrosis score, a new visual semi-quantitative staging system, was a predictor of mortality and the relationship between tomographic fibrosis score and respiratory function tests in patients with systemic sclerosis-associ- ated interstitial lung disease. The patients who have been followed up at a single-center rheumatology clinic for the last 5 years and met the American College of Rheumatology / European League Against Rheumatism (ACR-EULAR) 2013 systemic sclerosis classification criteria were included in the study. Clinical data were obtained retrospectively from patient records, including patients' characteristics, pulmonary function test (forced vital capacity), diffusing capacity of the lung for carbon monoxide test, high-reso- lution computed tomography results, medication history, and serological test results. High-resolution computed tomography of the patients diagnosed with interstitial lung disease were assessed for the study. The radiologists scored the extent of parenchymal abnormalities (ground glass opacification, reticulation, honeycombing, and consolidation) and calculated tomographic fibrosis score and also traction bronchiectasis score for each patient. Fifty-two patients (46 female, median age 60 (Q1-Q3:47-66) years) were included in this study. The median disease duration, follow-up time, interstitial lung disease duration, and time from sys- temic sclerosis diagnosis to interstitial lung disease diagnosis were 80 (59-143) months, 78 (50-119) months, 63 (43-81) months, and 4 (0-58) months, respectively. The median tomographic fibrosis score and traction bronchiectasis score of the patients were 3.08% (1.33-8.06) and 0 (0-2), respectively. There was a moderate direct correlation between tomographic fibrosis score and traction bronchiectasis score (r = +0.472, P < .001). Additionally, there was a mod- erate inverse correlation between tomographic fibrosis score and diffusing capacity of the lung for carbon monoxide at diagnosis (r = -0.554, P = .011). During the follow-up period, 12 (23%) patients died. Kaplan-Meier Test (P = 0.009) and Cox regression analysis (B: 4.673, 95% confidence interval, 1.321-16.529, P = .017) revealed that tomographic fibrosis score ≥ 5% was associated with mortality. Multivariate analysis was not performed due to the small number of patients. An inverse relationship was found between tomographic fibrosis score and diffusing capacity of the lung for carbon monoxide at diagnosis. The odds ratio for mortality was 4.7 when tomographic fibrosis score was ≥5%. Tomographic fibrosis score may be useful for predicting mor- tality and respiratory function in patients with systemic sclerosis-associated interstitial lung disease.

Cutaneous Manifestations, Clinical Characteristics, and Prognosis of Patients With Systemic Sclerosis Sine Scleroderma

Systemic sclerosis (SSc) sine scleroderma (ssSSc) is a subset of SSc defined by the absence of skin fibrosis. Little is known about the natural history and skin manifestations among patients with ssSSc. To characterize the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) within the EUSTAR database. This longitudinal observational cohort study based on the international EUSTAR database included all patients fulfilling the classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least 1 follow-up visit; ssSSc was defined by the absence of skin fibrosis (mRSS = 0 and no sclerodactyly) at all available visits. Data extraction was performed in November 2020, and data analysis was performed from April 2021 to April 2023. Main outcomes were survival and skin manifestations (onset of skin fibrosis, digital ulcers, telangiectasias, puffy fingers). Among the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as having ssSSc (mean [SD] age, 55.3 [13.9] years; 345 [91.8%] were female). At last available visit, in comparison with 708 patients with lcSSc and 708 patients with dcSSc with the same disease duration, patients with ssSSc had a lower prevalence of previous or current digital ulcers (28.2% vs 53.1% in lcSSc; P < .001; and 68.3% in dcSSc; P < .001) and puffy fingers (63.8% vs 82.4% in lcSSc; P < .001; and 87.6% in dcSSc; P < .001). By contrast, the prevalence of interstitial lung disease was similar in ssSSc and lcSSc (49.8% and 57.1%; P = .03) but significantly higher in dcSSc (75.0%; P < .001). Skin telangiectasias were associated with diastolic dysfunction in patients with ssSSc (odds ratio, 4.778; 95% CI, 2.060-11.081; P < .001). The only independent factor for the onset of skin fibrosis in ssSSc was the positivity for anti-Scl-70 antibodies (odds ratio, 3.078; 95% CI, 1.227-7.725; P = .02). Survival rate was higher in patients with ssSSc (92.4%) compared with lcSSc (69.4%; P = .06) and dcSSc (55.5%; P < .001) after up to 15 years of follow-up. Systemic sclerosis sine scleroderma should not be neglected considering the high prevalence of interstitial lung disease (>40%) and SSc renal crisis (almost 3%). Patients with ssSSc had a higher survival than other subsets. Dermatologists should be aware that cutaneous findings in this subgroup may be associated with internal organ dysfunction. In particular, skin telangiectasias in ssSSc were associated with diastolic heart dysfunction.

Audiovestibular Manifestations in Patients with Primary Raynaud's Phenomenon and Raynaud's Phenomenon Secondary to Systemic Sclerosis.

To address the prevalence of audiovestibular disorders in patients with primary Raynaud's Phenomenon (RP). A series of patients with primary RP and secondary RP in the context of systemic sclerosis (SSc) were compared with healthy controls. A prospective multicenter observational cross-sectional study was conducted in several Otolaryngology and Rheumatology Divisions of tertiary referral hospitals, recruiting 57 patients with RP and 57 age- and gender-matched controls. Twenty patients were classified as primary RP when unrelated to any other conditions and 37 patients who met the 2013 ACR/EULAR classification criteria for SSc were classified as having secondary RP associated with SSc. Audiometric and vestibular testing (vHIT), clinical sensory integration and balance testing (CTSIB), and Computerized Dynamic Posturography (CDP) were performed. As significant differences were found in the age of the two study groups, primary and secondary RP, no comparisons were made between both groups of RP but only with their control groups. No sensorineural hearing loss (SNHL) was recorded in any of our patients with primary RP and no differences were found in the voice audiometry tests with respect to controls. Four of 37 (10.8%) secondary RP patients presented SNHL. Those with SNHL were 7.03 times more likely to have a secondary RP than controls (p < 0.001). The audiometric curve revealed high-frequency hearing loss in 4 patients with RP secondary to SSc, and statistically significant differences were achieved when RP secondary was compared to controls in vHIT gain, caloric test, CTSIB, and CDP. Unlike patients with RP secondary to SSc, patients with primary RP do not show audiovestibular abnormalities. Regarding audiovestibular manifestations, primary RP can be considered a different condition than secondary RP.

P156 Evidence of Type I interferon activation during vascular manifestations of systemic sclerosis

Abstract Background/Aims Vascular involvement in systemic sclerosis (SSc) is known to start even before clinical diagnosis, driving digital ulcer (DU) disease. Later in the disease natural history, it can cause pulmonary artery hypertension (PAH) among other manifestations. Despite the proven immune origin of scleroderma, vascular involvement is not currently targeted by immune driven interventions. Similarly, few data are available on immune or inflammatory biomarkers and outcome measures of vascular disease in SSc. Digital artery volume index (DAVIX) has been recently proposed as an imaging surrogate outcome measure of vascular disease activity in SSc. Methods 86 patients attending our scleroderma program were consecutively enrolled for the evaluation of serum IFN score as previously described [2]. Clinical features, including presence or history of DUs, presence of PAH and DLCO, were recorded. DAVIX of the dominant hand’s fingers was calculated using time of flight magnetic resonance imaging analysed through IAG proprietary algorithm, as previously described [1]. Medians were compared by Mann-Whitney-Wilcoxon test; correlation with clinical parameters was performed using Spearman’s or Pearson test, as appropriate (R). Results 62 patients fulfilled the 2013 ACR/EULAR classification criteria for SSc (diffuse cutaneous 24.6%, limited cutaneous 75.4%), whereas 23 were classified as very early diagnosis of scleroderma (criteria score between 6 and 8). 23 patients had DU disease (history of DUs in the previous 24 weeks, presence of DUs at baseline assessment, or onset of new DUs during the following 24 weeks). 18 patients had reduced DLCO (&amp;lt;70) with FVC/DLCO&amp;gt;1.8 (suspected PAH). DAVIX showed a negative correlation with disease duration (r=-0.33 and p = 0.003) and with FVC/DLCO ratio (r=-0.34 and p = 0.009). Patients with DU disease presented lower DAVIX than patients without (p = 0.018). DAVIX showed a significant correlation with serum IFN score (r=-0.24, p &amp;lt; 0.032). Accordingly, patients classified as IFN-HI had lower DAVIX than those within the IFN-LO group (p = 0.016). Conclusion DAVIX correlated both with presence of DU disease, DLCO and disease duration. The correlation of DAVIX and serum IFN score does support the notion of innate immune involvement in vascular disease manifestations of SSc. Prospective testing in the context of randomised controlled trials will determine the value of DAVIX as a surrogate outcome measure of vascular disease severity in SSc. S. Di Donato: None. M. Hughes: None. K. Geloshi: None. E. De Lorenzis: None. V. Kakkar: None. R. Ross: None. P. O'Connor: None. O. Kubassova: Consultancies; Image Analysis Group CEO. F. Del Galdo: Grants/research support; Abbvie, AstraZeneca, Boeringher-Ingelheim, Capella, Chemomab, Janssen, Kymab, Mitsubishi-Tanabe.

Epidemiology and Survival of Systemic Sclerosis-Sarcoidosis Overlap Syndrome.

We evaluated the epidemiology, manifestations, serology, comorbidities, and survival among patients with systemic sclerosis (SSc) with and without sarcoidosis. We conducted a retrospective cohort study comparing patients with SSc with and without sarcoidosis. All patients fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc. Sarcoidosis was based on physician diagnosis and/or confirmatory biopsy. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier curves. We included 1977 patients (1971 with SSc, 6 with SSc-sarcoidosis) with a SSc-sarcoidosis prevalence of 0.30%. Sarcoidosis frequently preceded SSc (66.66%). The most frequent sarcoidosis manifestations were pulmonary (66.66%), lymphadenopathy (66.66%), arthritis (50%), cutaneous (33.33%), and hepatic (16.66%). Patients with SSc and SSc-sarcoidosis had female to male sex ratios of 4.5:1 vs 5:1 and median ages of SSc onset of 48.3 vs 43.8 years, respectively. Interstitial lung disease (35% vs 66.66%) and pulmonary hypertension (24.91% vs 50%) tended to occur more frequently whereas abnormal nailfold capillaries (34.7% vs 16.66%) and digital ulcers (33.33% vs 16.66%) tended to occur less frequently among patients with SSc-sarcoidosis, but the differences were not significant. There was an increased frequency of stroke among the patients with SSc-sarcoidosis (relative risk 8.59, 95% CI 1.02-72.00). The median survival times were 23.4 years for SSc-sarcoidosis and 18.6 years for SSc, with no differences in survival curves (log-rank test, P = 0.55). Sarcoidosis in SSc is rare but appears to occur more frequently than in the general population. It is associated with pulmonary, lymph node, cutaneous, joint, and hepatic involvement. Stroke occurs more frequently in patients with SSc-sarcoidosis but with no differences in survival.

Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis.

Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma. Autoimmune myositis is also a heterogeneous group of myopathies that classically encompass necrotizing myopathy, antisynthetase syndrome, dermatomyositis and inclusion body myositis. Recent data revealed that an additional disease subset, denominated "scleromyositis", should be recognized within both the systemic sclerosis and the autoimmune myositis spectrum. We performed an in-depth review of the literature with the aim of better delineating scleromyositis. Our review highlights that this concept is supported by recent clinical, serological and histopathological findings that have important implications for patient management and understanding of the disease pathophysiology. As compared with other subsets of systemic sclerosis and autoimmune myositis, scleromyositis patients can present with a characteristic pattern of muscle involvement (i.e. distribution of muscle weakness) along with multisystemic involvement, and some of these extra-muscular complications are associated with poor prognosis. Several autoantibodies have been specifically associated with scleromyositis, but they are not currently integrated in diagnostic and classification criteria for systemic sclerosis and autoimmune myositis. Finally, striking vasculopathic lesions at muscle biopsy have been shown to be hallmarks of scleromyositis, providing a strong anatomopathological substratum for the concept of scleromyositis. These findings bring new insights into the pathogenesis of scleromyositis and help to diagnose this condition, in patients with subtle SSc features and/or no autoantibodies (i.e. "seronegative" scleromyositis). No guidelines are available for the management of these patients, but recent data are showing the way towards a new therapeutic approach dedicated to these patients.

Роль капилляроскопии в оценке микроваскуляризации при ревматических заболеваниях

Nailfold capillaroscopy (NFC) is a non-invasive and safe tool for microvasculature assessment. Since its recent inclusion to classification criteria for systemic sclerosis (American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR), 2013) and monitoring disease progression, the importance of NFC in rheumatology has increased. Given its growing use by a variety of physicians worldwide, both in daily practice to differentiate primary and secondary Raynaud’s syndrome, and in the context of research to predict the progression of the disease and evaluate the treatment effectiveness, the description of the acquisition and analysis of capillaroscopic images remains relevant. This report provides information on the interpretation of NFC changes, particularly in systemic sclerosis and other rheumatic diseases.

Nailfold Capillaroscopy in Early Stages of Mixed Connective Tissue Disease in a Sample of Egyptian Patients

Introduction: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with a high titer of anti-U1 small nuclear ribonucleoprotein particles and a number of clinical pictures, mainly Raynaud's phenomenon. Nailfold capillaroscopy (NFC) is a noninvasive diagnostic tool for patients with different connective tissue diseases that permit detection of local microvascular changes that correlate with systemic vascular involvement. Aim of the Study: The aim of this study was to compare the results of NFC in patients with systemic sclerosis (SSc) and MCTD to determine the chief characteristics of skin microangiopathy in early MCTD and attempt to describe a characteristic MCTD pattern in Egyptian patients. Methodology: This cross-sectional study included forty patients diagnosed with MCTD according to Alarcón-Segovia and Villareal criteria and twenty patients with confirmed systemic sclerosis according to the American College of Rheumatology and the European League against Rheumatism classification criteria for Systemic Sclerosis. Nailfold examination for the study subjects was performed describing architectural derangement, capillary density changes, mega capillary and enlarged loops, microhemorrhages, and angiogenesis. Results: Of the sixty patients studied, 49 (81.7%) patients were females and 11 were males with a mean age of 31 years with a median of 29.5 and range 16–52 years. Three of the twenty patients diagnosed with systemic sclerosis had arthritis. Out of sixty patients, 53.3% had thickened skin, 19 patients exhibited puffy fingers, six patients showed rash, and none had swollen joints. The skin was significantly thicker in systemic sclerosis patients (85%) compared to 37.5% in the MCTD population. Patients presented with various features, the most common of which was fatigue (26.7%) and myositis (23% of patients). There is a significant negative correlation of −0.508 (P = 0.022) between the enlargement scores and illness duration in systemic sclerosis patients. Those patients also exhibited a statistically significant positive correlation of 0.520 (P = 0.019) between hemorrhage score and the number of tender joints. Alternatively, patients diagnosed with MCTD exhibited a significant positive correlation between the architectural changes scores of their joints and both the duration of their illness (0.347; P = 0.028) and the number of swollen joints (0.424; P = 0.006). MCTD patients also showed a significant correlation of 0.423 (P = 0.007) between their hemorrhage scores and their age at the time of the study. Conclusion: In this study, the results obtained were qualitatively satisfactory for clear delineation of the nailfold capillaries features in MCTD. Therefore, it aids in the recognition of alternations in nailfold capillaries making an early prediction of course of illness in MCTD patients possible and suggests a potential ability to differentiate from early SSc, thus helps in preventing morbidities and sequelae of the disease.

Functional disability and health-related quality of life among systemic sclerosis patients in Bangladesh

ObjectiveTo assess the relationship between functional disability and health-related quality of life (HRQoL) among systemic sclerosis (SSc) patients.MethodologyThis cross-sectional study was carried out on 78 adults who met the classification criteria for SSc defined by the American College of Rheumatology/European League of Rheumatology (ACR/EULAR)-2013. The Bangla version of Short Form 36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were used to measure HRQoL and functional disability in SSc patients.ResultsThe patients' median [IQR] HAQ-DI was 1.4 [0.6–2.1], with 37.2% having a mild functional disability, 33.3 percent having a moderate functional disability, and 29.5 percent having a severe functional disability. The hygiene and activity domains of the HAQ-DI obtained the highest scores, 2.0 [0.0–3.0] and 2.0 [1.0–3.0], respectively. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36 had median [IQR] values of 26.2 [15.0–58.1] and 42.0 [19.6–60.6]. The highest score was 50.0 [25.0–75.0] in social functioning. The PCS of the SF-36 was moderately correlated with the HAQ-DI (rs = − 0.629, P < 0.001) and the MCS of the SF-36 was weakly correlated with the HAQ-DI ((rs = − 0.344, P < 0.001). Age, female sex, and incomplete fist closure substantially influenced functional status. Calcinosis, Raynaud's Phenomenon, and flexion contracture significantly diminished the quality of life.ConclusionsFunctional disability negatively affects health-related quality of life. Age, Musculoskeletal, and skin involvement are significantly associated with poor quality of life and functional disability. Therefore, treatment strategies should be aimed at reducing functional disability, which will enhance the HRQoL of SSc patients.